Pancreatic cancer is one of the most lethal human cancers, where the death rate nearly equals the incidence. Beyond surgery and gemcitabine, there is no "gold standard" for the treatment of pancreatic cancer. Gemcitabine offers the best potential for improving survival, but while the potential for palliation is well-documented, within months of treatment, there is inevitably failure, with either local tumor progression or new metastatic disease. Because of this lack of appropriate therapy, patients with locally advanced disease are an ideal population for the study of novel agents. Traditional Chinese medicine (TCM) is practiced around the world and is often used in the treatment of cancer either alone or in combination with western medicine. Many important chemotherapy agents have been derived from TCM and there is extensive preclinical evidence for the pharmacological activity of different TCM products on cancer growth. However, much of the research lacks appropriate methodologies of clinical investigation including randomization, control groups, and blinding, as well as lack of documentation on compliance and outcomes. One TCM product that has been used for over 1000 years in China and other Asian countries is Chan su, the dried toad venom or the dried secretion from the skin glands of Bufo bufo gargarizans Cantor or B. melanotictus Schneider. Preclinical studies of huachansu, the water extract of Chansu, conducted in China and at The University if Texas M. D. Anderson Cancer Center and clinical studies conducted in China clearly suggest that huachansu is an appropriate compound worth further exploration. At the present time, however, no trials have been conducted on a sufficient scale and with proper methodology to fully evaluate huachansu. The proposed study will be a randomized, double-blind, placebo-controlled, phase II clinical trial for patients with pancreatic cancer to assess the efficacy based on tumor response and 6-month survival, safely and toxicity, and changes in quality of life. Huachansu will be given along with gemcitabine, a commonly used conventional chemotherapy for pancreatic cancer, and radiotherapy. Patients will be randomized to either receive gemcitabine, radiotherapy, and huachansu or gemcitabine, radiotherapy, and placebo. We will also monitor patient blood levels of the three main cardiac glycosides that are in huachansu (bufalin, cinobufagin, and resibufogenin). This information will provide evidence to delineate the role of these cardiac glycosides in antitumor activity. [unreadable] [unreadable]